Background
A significant number of women are diagnosed with minor cytologi
cal abnormalities on cervical screening. Many authorities recom
mend
surveillance as spontaneous regression might occur. However,
attendance for cytological follow-up decreases with time and mig
ht put
some women at risk of developing invasive disease.
Objectives
To assess the optimum management strategy for women with min
or cervical cytological abnormalities (atypical squamous cells of
undetermined significance - ASCUS or low-grade squamous intra-e
pithelial lesions - LSIL) at primary screening in the absence o
f HPV
(human papillomavirus) DNA test.
Search methods
We searched the following electronic databases: Cochrane Cent
ral Register of Controlled Trials (CENTRAL Issue 4 2016), MEDL
INE,
and Embase from inception to 21 April 2016.
Selection criteria
We included randomised controlled trials (RCTs) comparing imme
diate colposcopy to cytological surveillance in women with atyp-
ical squamous cells of undetermined significance (ASCUS/borderl
ine) or low-grade squamous intra-epithelial lesions (LSIL/mi
ld
dyskaryosis).
Data collection and analysis
The primary outcome measure studied was the occurrence of cervical
intra-epithelial neoplasia (CIN). The secondary outcome measur
es
studied included default rate, clinically significant anxiety a
nd depression, and other self-reported adverse effects.
We classified studies according to period of surveillance, at 6, 1
2, 24 or 36 months, as well as at 18 months, excluding a possible
exit-examination. We calculated pooled risk ratios (RR) and 95%
confidence intervals (CI) using a random-effects model with inver
se
variance weighting. Inter-study heterogeneity was assessed
with I
2
statistics.
Main results
We identified five RCTs with 11,466 participants that fulfilled
the inclusion criteria. There were 18 cases of invasive cervical ca
ncer,
seven in the immediate colposcopy and 11 in the cytological surve
illance groups, respectively. Although immediate colposcopy d
etects
CIN2+ and CIN3+ earlier than cytology, the differences were no
longer observed at 24 months (CIN2+: 3 studies, 4331 women;
17.9% versus 18.3%, RR 1.14, CI 0.66 to 1.97; CIN3+: 3 studies
, 4331 women; 10.3% versus 11.9%, RR 1.02, CI 0.53 to 1.97). The
inter-study heterogeneity was considerable (I
2
greater than 90%). Furthermore, the inclusion of the results o
f the exit examinations
at 24 months, which could inflate the CIN detection rate of cytolog
ical surveillance, may have led to study design-derived bias; w
e
therefore considered the evidence to be of low quality.
When we excluded the exit examination, the detection rate of hig
h-grade lesions at the 18-month follow-up was higher after imme
diate
colposcopy (CIN2+: 2 studies, 4028 women; 14.3% versus 10.1%, R
R 1.50, CI 1.12 to 2.01; CIN3+: 2 studies, 4028 women, 7.8%
versus 6.9%, RR 1.24, CI 0.77 to 1.98) both had substantial in
ter-study heterogeneity (I
2
greater than 60%) and we considered the
evidence to be of moderate quality).
The meta-analysis revealed that immediate referral to colpos
copy significantly increased the detection of clinically insignifi
cant cervical
abnormalities, as opposed to repeat cytology after 24 months
of surveillance (presence of koilocytosis: 2 studies, 656 women
; 32%
versus 21%, RR 1.49, 95% CI 1.17 to 1.90; moderate-quality evi
dence); incidence of any CIN: 2 studies, 656 women; 64% versus
32%, RR 2.02, 95% CI 1.33 to 3.08, low-quality evidence; inciden
ce of CIN1: 2 studies, 656 women; 21% versus 8%, RR 2.58, 95%
CI 1.69 to 3.94, moderate-quality evidence).
Due to differences in trial designs and settings, there was la
rge variation in default rates between the included studies.
The risk for
default was higher for the repeat cytology group, with a four-f
old increase at 6 months, a six-fold at 12 and a 19-fold at 24 month
s
(6 months: 3 studies, 5117 women; 6.3% versus 13.3%, RR 3.85, 9
5% CI 1.27 to 11.63, moderate-quality evidence; 12 months: 3
studies, 5115 women; 6.3% versus 14.8%, RR 6.39, 95% CI 1.24 t
o 32.95, moderate-quality evidence; 24 months: 3 studies, 433
1
women; 0.9% versus 16.1%, RR 19.1, 95% CI 9.02 to 40.43, moder
ate-quality evidence).
Authors’ conclusions
Based on low- or moderate-quality evidence using the GRADE app
roach and generally low risk of bias, the detection rate of CIN2
+
or CIN3+ after two years does not appear to differ between imm
ediate colposcopy and cytological surveillance in the absence of H
PV
testing, although women may default from follow-up. Immedia
te colposcopy probably leads to earlier detection of high-grade
lesions,
but also detects more clinically insignificant low-grade lesions
. Colposcopy may therefore be the first choice when good compliance
is
not assured. These results emphasize the need for an accurate r
eflex HPV triage test to distinguish women who need diagnosti
c follow-
up from those who can return safely to routine recall.